Abstract
Valve-in-valve transcatheter aortic valve replacement is an established alternative to conventional surgical reoperation for failed aortic bioprosthetic valves. The technique has undergone significant refinements in recent years, aiming to tackle pain points of the procedure such as subpar hemodynamics and coronary obstruction. In this state-of-the-art review, we aim to discuss these refinements, including novel surgical valves, transcatheter heart valve positioning, bioprosthetic valve fracture, and prevention of coronary obstruction, among others. We also summarize key updates on clinical trial data and contemporary outcomes of valve-in-valve transcatheter aortic valve replacement.
Introduction
Valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) consists of the implantation of a transcatheter heart valve (THV) in a failed bioprosthetic surgical heart valve (SHV). This procedural modality represents an alternative to redo surgery and is increasingly used to treat degenerated SHVs. Although ViV procedures may be performed in all valve positions, , they are most commonly performed in the aortic position (ViV TAVR). In this review, we will explore the latest updates in the literature related to aortic ViV TAVR, including procedural trends, technical planning, prevention of complications, and future directions.
Preprocedural Aspects of ViV
Types of Surgical Heart Valves
A shift in surgical practice favoring bioprosthetic over mechanical SHVs has been well-described. A 2015 study from the United States National Inpatient Sample showed that, while bioprosthetic SHVs represented only around 38% of surgically implanted aortic valves between 1998 and 2001, their share grew to around 64% between 2007 and 2011. This growth was present in all age groups but was most marked in patients aged 55 to 64 years. In this age group, bioprosthetic SHVs represented 10% to 20% of all implants at the beginning of the 2000s, growing to approximately 50% by 2010. This trend is not exclusive to the United States. A study from a major nationally representative French database showed that between 2007 and 2022, for every patient receiving a mechanical aortic SHV, seven received a bioprosthetic SHV. Reasons behind this trend include similar outcomes in patients receiving mechanical and bioprosthetic valves and guideline support for shared decision-making for patients selecting their type of valve.
Although bioprosthetic SHVs mitigate the bleeding risk associated with long-term anticoagulation, they are subject to structural valve deterioration (SVD). This shift in surgical practice in favor of bioprosthetic SHVs, in conjunction with indication expansion and refinement of TAVR, has resulted in an increase in the number of ViV TAVR procedures to treat degenerated surgical valves ( Figure 1 ).
Bioprosthetic SHVs vary significantly in their design and tissue composition. One of the key differences between surgical valves, as it relates to ViV TAVR, is whether they are stented (i.e., with rigid struts supporting the leaflets) or stentless (i.e., without struts) ( Figure 2 ). ViV TAVR in stented and stentless SHV has been compared in the Valve-in-Valve International Data (VIVID) Registry. Stentless valves fail more frequently with regurgitation, whereas stented ones fail predominantly with stenosis. Stentless valves also do not have fluoroscopic markers to aid in visualization of the landing zone, which can make accurate positioning of a THV device difficult and may explain higher rates of THV embolization in the VIVID Registry. Finally, stentless SHVs are associated with an increased risk of coronary obstruction, a potentially lethal complication. , This is due to increased displacement of the leaflets after expansion of the THV, as there is no limitation on their movement by the stents. A similar phenomenon may also be seen in stented valves with externally mounted leaflets (such as the Mitroflow [Livanova plc, London, United Kingdom] and the recently discontinued Trifecta [Abbott Laboratories, Abbott Park, IL]), which also have higher rates of coronary obstruction. ,
While all bioprosthetic SHVs are expected to eventually fail, the rate at which they do varies. Lack of a standardized definition of SVD across studies has made comparisons of valve durability difficult. The Valve Academic Research Consortium 3 definitions should make comparisons across trials more uniform ( Table 1 ). With those limitations in mind, valves such as the Perimount (Edwards Lifesciences, Irvine, CA) and the Hancock (Medtronic Inc, Minneapolis, MN) have an established track record of long durability established in single-center studies using surrogate markers of SVD such as reintervention. , Others, such as the Mitroflow, have a mean time to structural valve degeneration of only about 4 years, while the Trifecta has been withdrawn from the market due to concerns about the risk of early SVD.
| Bioprosthetic valve degeneration categories | Clinical presentation | Stages of deterioration |
|---|---|---|
| SVD : intrinsic permanent changes to the prosthetic valve; includes wear and tear, leaflet disruption, flail leaflet, fibrotic leaflet/calcification, strut fracture | Subclinical → any bioprosthetic dysfunction associated without hemodynamic changes and absence of symptoms | Stage 1: Morphological degeneration
|
| Non-SVD : nonintrinsic valve dysfunction. i.e., residual intra-/para-prosthetic regurgitation; pannus/suture entrapping of leaflets; inappropriate positioning or sizing; aortic root dilatation; PPM; embolization | Bioprosthetic valve failure stage 1: Any bioprosthetic valve dysfunction associated with clinically expressive criteria (new/worsening symptoms, LV dilation/hypertrophy/dysfunction, or pulmonary hypertension) OR irreversible stage 3 hemodynamic valve deterioration. Bioprosthetic valve failure stage 2: aortic valve reoperation or reintervention Bioprosthetic valve failure stage 3: valve-related death. | Stage 2: Moderate hemodynamic valve deterioration
|
Thrombosis : defined as clinical sequelae of a thromboembolic event or worsening AS/AR and
| Stage 3: Severe hemodynamic valve deterioration
| |
| Endocarditis : Fulfilling Duke endocarditis criteria ; evidence of abscess/pus/vegetation confirmed on histological/microbiological studies during reoperation ; Criteria in 2 confirmed during autopsy |
Newer surgical valve designs are incorporating features that may increase durability and enable ViV TAVR when failure occurs. For example, the Inspiris valve (Edwards Lifesciences) contains leaflets that are treated with a new preservation technology known as Resilia that has shown decreased tissue calcification in in vivo models. This valve also incorporates fluoroscopically visible size markers and an expandable valve frame. The ends of the cobalt-chromium alloy band are secured by a polyester shrink-sleeve in sizes 19 to 25 mm, allowing the internal orifice of the valve to expand during ViV TAVR with a balloon-expandable valve.
The 5-year outcomes of the COMMENCE trial, a prospective investigation of a Perimount variation with Resilia tissue technology (i.e., not the Inspiris valve), are encouraging, with 98.7% freedom from reintervention and good hemodynamics. A registry with 488 Inspiris patients has also shown greater freedom from readmission and better hemodynamics at 2 years when compared with the Magna Ease surgical valve (Edwards Lifesciences). However, a handful of cases of ViV with the Inspiris valve have already been reported. In two of the reported cases, the valve did demonstrate enlargement with ballooning. , In the third case, the valve did not appear to expand as expected. It still remains to be seen whether changes in surgical valve design will result in improved durability and facilitate future ViV procedures.
Small SHVs, Pre-ViV Mismatch
High-residual gradients after ViV TAVR have been identified as the “Achilles’ heel” of the procedure. A previous analysis of the VIVID Registry showed that the two most important determinants of long-term procedural outcomes were the size and the mode of failure of the original SHV. Patients with stenosis as the mode of failure and valve label size <21 mm had significantly worse survival when compared to patients with regurgitation or intermediate/large valve sizes. In that study, as many as a quarter of the patients had a postprocedural mean gradient ≥20 mmHg. Similarly, in the PARTNER 2 ViV Registry, over a third of patients had elevated residual gradients, a finding that was associated with increased mortality at 1 year (16.7% in patients with gradients ≥20 mmHg vs. 7.7% in others; hazard ratio [HR] 2.27, 95% CI 1.16-4.46; p = 0.01).
Mechanistically, elevated residual gradients in ViV procedures are related to the “Matryoshka effect” committing operators to insert progressively smaller THVs within the initial surgical valve. The true internal diameter (ID), a caliper measure of the inflow of the SHV, is more important for procedural planning than the label size, as this will determine the true area for expansion of the THV device. When the size of the SHV is small (i.e., true ID <21 mm), the effective orifice area after ViV TAVR is even smaller, which can lead to patient prosthesis mismatch (PPM), underexpansion of the THV, and high-residual gradients. Of importance, SHVs with the same label size may actually have very different internal areas due to how the leaflets are constructed in relation to the frame of the valve. For example, a Hancock 21 mm valve has a true ID of 17 mm, whereas a Perimount Magna 21 mm has a true ID of 19 mm.
In patients with degenerated SHV and pre-existent PPM (severe PPM is defined as an effective orifice area (EOA) ≤ 0.65 cm 2 /m 2 for patients with a body mass index < 30 kg/m 2 , and ≤0.55 cm 2 /m 2 for those with body mass index ≥30 kg/m 2 ), ViV TAVR is unlikely to result in sustained hemodynamic improvement and is associated with increased risk of mortality and adverse outcomes. , Investigators of the VIVID Registry showed that in a cohort of 1168 aortic ViV patients, around 7.6% of patients had severe pre-ViV PPM (as ascertained by standardized tables with EOAs for each surgical valve model and size). Severe pre-ViV PPM was associated with higher postprocedural gradients (47.9 vs. 29.6% in patients without PPM) and an increased adjusted risk for 1-year mortality (HR 1.88, 95% CI 1.07-3.28). In addition, patients who received a balloon-expandable valve who had severe pre-ViV PPM developed elevated residual gradients much more frequently (78.3 vs. 33.9% in those with severe pre-ViV PPM and self-expandable valves; p < 0.001). In the long-term dataset of the VIVID Registry, small true ID was identified as a predictor of increased long-term mortality, and pre-ViV PPM was shown to be a correlate of all-cause reintervention. In such patients, procedural adjuncts, such as bioprosthetic valve fracture (BVF) or redo surgery, need to be considered.
Procedural Aspects of ViV
Transcatheter Valve Selection in ViV TAVR
Similar to SHV, THV has significant variations in design that can affect hemodynamic performance. The functional area of self-expandable THV (SEV) can be either located above the aortic valve annulus (Evolut [Medtronic Inc] family) or at the level of the annulus (Navitor [Abbott Inc]). All balloon-expandable transcatheter heart valves (BEV) are intra-annular (SAPIEN 3, SAPIEN 3 Ultra, SAPIEN X4 [Edwards Lifesciences]; MyVal [Meril Life, Vapi, India]). SEV valves have consistently shown better hemodynamic results in aortic ViV. In the VIVID experience, cases performed with the Evolut family of valves had both lower postprocedural gradients (14.7 ± 8.2 mmHg vs. 17.7 ± 9.5 mmHg; p < 0.001) and larger EOAs (1.59 ± 0.50 cm 2 vs. 1.39 ± 0.51 cm 2 ; p < 0.001). In the LYTEN trial, the only randomized trial in aortic ViV, similar hemodynamic results were found with lower gradients among patients receiving SEV (14 ± 7 mmHg for SEV vs. 22 ± 8 mmHg for BEV; p < 0.001). However, it is unclear if these differences in postprocedural gradients translate into clinical benefits.
Valve Positioning and Deformation
Implantation technique is an important determinant of hemodynamic performance in ViV TAVR procedures. High THV implantation (i.e., a more aortic position in relation to the surgical sewing ring) results in increased EOA and improved hemodynamics, likely from sparing the functional area of the device from being underexpanded by the surgical valve ring ( Figure 3 ). The benefits of high positioning for BEV and SEV valves have been shown both in vitro , and in the clinical setting. , In a core lab analysis of 113 ViV cases with SAPIEN 3, patients with high implantation depth had a 4% rate of combined elevated gradients or need for a pacemaker, compared with 50% in cases with deep implantation ( p < 0.001). A higher ventricular implantation depth was a predictor for both elevated gradients (odds ratio [OR] 4.45, 95% CI 1.05-19; p = 0.04) and pacemaker requirement (OR 8.1, 95% CI 1.38-47.8; p = 0.02). For BEV, the “central marker method,” where the central marker of SAPIEN 3 is positioned 3 to 6 mm above the ring of the surgical valve was associated with better hemodynamics than the “top stent method,” whereby the top of the BEV is aligned with the top of the surgical posts in the SHV.
A novel concept that has been recently developed relates to deformation of the THV. , Given the limited space afforded by the surgical valve, poor expansion of the transcatheter valve may occur. Investigators performed a core lab study of 53 self-expandable aortic ViV patients who underwent computed tomography (CT) scan evaluation 30 days after the procedure. They showed that higher positioning of the THV was associated with improved expansion of the prosthesis waist and leaflets. Consequently, they identified that proper expansion at the prosthesis waist predicted lower gradients and larger EOAs. In the same study, oversizing of the Evolut prosthesis with a 26 mm device in small surgical valves was associated with better hemodynamics when compared to undersizing (23 mm) when implanted in a high position, a finding that had already been suggested by prior in vitro work. Therefore, operators should consider the effects of valve type, size, and implantation depth when planning ViV TAVR procedures.
Bioprosthetic Valve Fracture
An area that has received considerable attention in recent years is BVF. The goal of BVF is to intentionally disrupt the sewing ring of the SHV by inflating noncompliant balloons at high pressure ( Figure 4 ). Most, but not all, SHVs are amenable to BVF. SHVs are typically made of metallic stent frames or polymeric stent frames. Metallic stent frames require high pressure to fracture, and they typically show better expansion of the THV, whereas polymeric stent frames can be fractured at lower pressures but are subject to elastic recoil. Table 2 displays SHV and thresholds for fracture with BVF during bench testing.
